Objective To characterize trafficking of lymphocyte subsets in the intrathecal compartment and the factors that influence the presence of free-flowing cells in cerebrospinal fluid. An understanding of cell trafficking in the intrathecal compartment is important for evaluating inflammatory diseases of the central nervous system, and has taken on new significance because the CNS is an important reservoir of HIV infection. We have developed a number of special techniques for characterizing lymphocyte subsets in the CSF of healthy monkeys, and have assessed several factors that influence the number of cells present in the intrathecal compartment. Perhaps the most exciting discovery was that monkeys exposed to a serotonergic drug in infancy -- fluoxetine -- have a chronic up-regulation of the number of cells circulating in CSF, lasting for several years after the termination of drug treatment. These studies have provided a substantial normative data base in the healthy host for comparison with various disease conditions. Key words cerebrospinal fluid, T lymphocytes, cell trafficking